Cholesterol is central to pancreatic β-cell physiology and alterations of its homeostasis contribute to β-cell dysfunction and diabetes. Proper intracellular cholesterol levels are maintained by different mechanisms including uptake via the low-density lipoprotein receptor (LDLR). In the liver, the proprotein convertase subtilisin/kexin type 9 (PCSK9) routes the LDLR to lysosomes for degradation, thus limiting its recycling to the membrane. PCSK9 is also expressed in the pancreas and loss of function mutations of PCSK9 result in higher plasma glucose levels and increased risk of Type 2 diabetes mellitus. Aim of this study was to investigate whether PCSK9 also impacts β-cells function.

Pancreatic PCSK9 controls the organization of the β-cell secretory pathway via LDLR-cholesterol axis / A. Marku, L. Da Dalt, A. Galli, N. Dule, P. Corsetto, A.M. Rizzo, A. Moregola, P. Uboldi, F. Bonacina, P. Marciani, M. Castagna, A.L. Catapano, G.D. Norata, C. Perego. - 136:(2022 Nov), pp. 155291.1-155291.11. [10.1016/j.metabol.2022.155291]

Pancreatic PCSK9 controls the organization of the β-cell secretory pathway via LDLR-cholesterol axis

A. Marku
Primo
;
L. Da Dalt
Secondo
;
N. Dule;P. Corsetto;A.M. Rizzo;A. Moregola;P. Uboldi;F. Bonacina;P. Marciani;M. Castagna;A.L. Catapano;G.D. Norata
Penultimo
;
C. Perego
Ultimo
2022

Abstract

Cholesterol is central to pancreatic β-cell physiology and alterations of its homeostasis contribute to β-cell dysfunction and diabetes. Proper intracellular cholesterol levels are maintained by different mechanisms including uptake via the low-density lipoprotein receptor (LDLR). In the liver, the proprotein convertase subtilisin/kexin type 9 (PCSK9) routes the LDLR to lysosomes for degradation, thus limiting its recycling to the membrane. PCSK9 is also expressed in the pancreas and loss of function mutations of PCSK9 result in higher plasma glucose levels and increased risk of Type 2 diabetes mellitus. Aim of this study was to investigate whether PCSK9 also impacts β-cells function.
Cholesterol; Diabetes; Glucose homeostasis; Insulin; LDLR; PCSK9; Animals; Blood Glucose; Calcium; Cholesterol; Insulin; Lipoproteins, LDL; Mice; Mice, Knockout; Pancreas; Proinsulin; Receptors, LDL; SNARE Proteins; Secretory Pathway; Serine Endopeptidases; Subtilisins; Diabetes Mellitus, Type 2; Proprotein Convertase 9;
Settore BIO/14 - Farmacologia
Settore BIO/09 - Fisiologia
DECC18ACORS_01 - Dipartimenti di Eccellenza 2018-2022 - Dipartimento di SCIENZE FARMACOLOGICHE E BIOMOLECOLARI - CORSINI, ALBERTO - DECC - Bando Dipartimenti di Eccellenza - 2018
PRIN201719GNORA_01 - Integrating metabolism and immunity: cellular and molecular pathways leading to metabolic dysregulation and autoimmunity - NORATA, GIUSEPPE DANILO - PRIN2017 - PRIN bando 2017 - 2019
PRIN201719ACATA_01 - Low density lipoprotein receptor (LDLR)-independent effects of proprotein convertase subtilisin/kexin type 9 (PCSK9): role in modulating insulin-resistance, ectopic fat accumulation and low-grade inflammation - CATAPANO, ALBERICO LUIGI - PRIN2017 - PRIN bando 2017 - 2019
CAR_RIC20FBONA_01 - Molecular mechanisms of T regulatory impairment in Familial Hypercholesterolemia: exploring cellular metabolic reprogramming as a tool to restore theirsuppressive function - BONACINA, FABRIZIA - CAR_RIC - Bandi Fondazione Cariplo - 2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/944811
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